Neoplasia of the large bowel, colon or rectum is one of the most common forms of cancer, second only to lung cancer as a cause of cancer death in the United States. The etiology for most cases of large bowel cancer appears to be environmental, with much research having been focused on dietary links to cancer of the colorectum. Although as many as 25% of patients with colorectal cancer may have a family history of the disease (most evident in Familial Adenomatous Polyposis (FAP) or Hereditary Non-Polyposis Colon Cancer (HNPCC)) the majority of patients have no such family history and are said to have sporadic neoplasia. Once a tumor has been detected, treatment involves surgical removal of the tumor and often large portions of the affected colon.
Dietary alteration has been well studied as a method to reduce the risk of colon cancer. Although two of the risk factors for development of the disease were thought to be ingestion of high levels of animal fat and ingestion of a diet low in fiber, clinical trials have shown that reduction in dietary fat and increases in dietary fiber may not reduce the risk of colorectal neoplasia. Other efforts at reducing the risk of development of colon cancer have focused on intake of calcium supplements, which may inactivate bowel carcinogens through formation of insoluble soaps (Mayer (1994) In: Harrison's Principles of Internal Medicine, Chapter 257, pgs. 1424-1428) or may affect cancer risk through effects mediated by the extracellular calcium sensing receptor (Lamprecht and Lipkin (2001) Annals New York Academy of Sciences 952:73-87).
Aspirin (acetylsalicylic acid), an inhibitor of arachidonic acid metabolism, has been shown to inhibit the growth of colon tumors in rodents. Studies have also suggested that aspirin use is protective against carcinogenesis in the large bowel (Greenberg, et al. (1993) J. Natl. Cancer Inst. 85:912-916; Giovannucci, et al. (1995) New Engl. J. Med. 333:609-14; Thun, et al. (1991) New Engl. J. Med. 325:1593-1596). Several studies have also shown that sulindac, a non-steroidal anti-inflammatory drug, may have use as a preventative treatment for hereditary polyposis of the colon and rectum (Labayle, et al. (1991) Gastroenterology 101:635-639; Ladenheim, et al. (1995) Gastroenterology 108:1083-1087; Giardiello, et al. (1993) New Engl. J. Med. 328:1313-1316). However, there remains a need for substances that can prevent colon cancer in humans.